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Recombinant adeno-associated viral vector (rAAV) delivery of GDNF provides protection against 6-OHDA lesion in the common marmoset monkey (Callithrix jacchus)
被引:83
作者:
Eslamboli, A
Cummings, RM
Ridley, RM
Baker, HF
Muzyczka, N
Burger, C
Mandel, RJ
Kirik, D
Annett, LE
机构:
[1] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England
[2] Univ Florida, Coll Med, McKnight Brain Inst, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA
[3] Univ Florida, Coll Med, Gene Therapy Ctr, Gainesville, FL 32610 USA
[4] Univ Florida, McKnight Brain Inst, Dept Neurosci, Gainesville, FL 32610 USA
[5] Univ Florida, Coll Med, Powell Gene Therapy Ctr, Gainesville, FL 32610 USA
[6] Lund Univ, Wallenberg Neurosci Ctr, Dept Physiol Sci, Div Neurobiol, S-22184 Lund, Sweden
[7] Univ Hertfordshire, Dept Psychol, Hatfield AL10 9AB, Herts, England
关键词:
glial cell line-derived neurotrophic factor;
Parkinson's disease;
marmoset monkey;
neuroprotection;
behaviour;
gene therapy;
adeno-associated viral vector;
D O I:
10.1016/j.expneurol.2003.08.007
中图分类号:
Q189 [神经科学];
学科分类号:
071006 ;
摘要:
Glial cell line-derived neurotrophic factor (GDNF) has shown potential as a treatment for Parkinson's disease. Recombinant adeno-associated viral vectors expressing the GDNF protein (rAAV-GDNF) have been used in rodent models of Parkinson's disease to promote functional regeneration after 6-OHDA lesions of the nigrostriatal system. The goal of the present study was to assess the anatomical and functional efficacy of rAAV-GDNF in the common marmoset monkey (Callithrix jacchus). rAAV-GDNF was injected into the striatum and substantia nigra 4 weeks prior to a unilateral 6-OHDA lesion of the nigrostriatal bundle. Forty percent of the dopamine cells in the lesioned substantia nigra of the rAAV-GDNF-treated monkeys survived, compared with 21% in the untreated monkeys. Fine dopaminergic fibres were observed microscopically in the injected striatum of some rAAV-GDNF-treated monkeys, suggesting that rAAV-GDNF treatment may have prevented, at least in part, the loss of dopaminergic innervation of the striatum. Protection of dopamine cells and striatal fibre innervation was associated with amelioration of the lesion-induced behavioural deficits. rAAV-GDNF-treated monkeys showed partial or complete protection not only in the amphetamine and apomorphine rotation but also in head position and the parkinsonian disability rating scale. Therefore, our study provides evidence for the behavioural and anatomical efficacy of GDNF delivered via an rAAV vector as a possible treatment for Parkinson's disease. (C) 2003 Elsevier Inc. All rights reserved.
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页码:536 / 548
页数:13
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